I think the more important question to resolve here is: did AlphaFold change anything with respect to structure prediction that enabled them to make accurate predictions in the complete absence of sequence similarity to proteins with known structure?
My understanding is no, they did the equivalent of template modelling, which uses sequence/structure relationships (that are more subtle than the ones you get from homology modelling).
I'm less interested in reconciling my internal mental model of psp wiht CASPs, than I am in understanding if AF2 is somehow able to get all the necessarily structural constraints through coevolution of amino acid pairs entirely without some (direct or indirect) learned relationship between the sequence similarity to known structures (be it even short fragments like helices).
If they really did do that, and nobody did it before, that's great and I will happily promote the DM work, as it supports what I said when I did CASP: ML and MD will eventually win, although in a way that exploits the rich sequence evolutionary information we have, rather than predominantly by having an accurate force field and good smapling methods.
My understanding is no, they did the equivalent of template modelling, which uses sequence/structure relationships (that are more subtle than the ones you get from homology modelling).
I'm less interested in reconciling my internal mental model of psp wiht CASPs, than I am in understanding if AF2 is somehow able to get all the necessarily structural constraints through coevolution of amino acid pairs entirely without some (direct or indirect) learned relationship between the sequence similarity to known structures (be it even short fragments like helices).
If they really did do that, and nobody did it before, that's great and I will happily promote the DM work, as it supports what I said when I did CASP: ML and MD will eventually win, although in a way that exploits the rich sequence evolutionary information we have, rather than predominantly by having an accurate force field and good smapling methods.